Reactions of Alkenes

Addition Reactions of Alkenes

The most common chemical transformation of a carbon-carbon double bond is theaddition reaction. A large number of reagents, both inorganic and organic, have been found to add to this functional group, and in this section we shall review many of these reactions. A majority of these reactions areexothermic, due to the fact that the C-C pi-bond is relatively weak (ca. 63 kcal/mole) relative to the sigma-bonds formed to the atoms or groups of the reagent. Remember, the bond energies of a molecule are the energies required to break (homolytically) all the covalent bonds in the molecule. Consequently, if the bond energies of the product molecules are greater than the bond energies of the reactants, the reaction will be exothermic. The following calculations for the addition of H-Br are typical. Note that by conventionexothermic reactions have a negative heat of reaction.

1. Addition of Strong Brønsted Acids

As illustrated by the preceding general equation, strong Brønsted acids such as HCl, HBr, HI & H2SO4, rapidly add to the C=C functional group of alkenes to give products in which new covalent bonds are formed to hydrogen and to the conjugate base of the acid. Using the above equation as a guide, write the addition products expected on reacting each of these reagents with cyclohexene.

Weak Brønsted acids such as water (pKa= 15.7) and acetic acid (pKa= 4.75) do not normally add to alkenes. However, the addition of a strong acid serves to catalyze the addition of water, and in this way alcohols may be prepared from alkenes. For example, if sulfuric acid is dissolved in water it is completely ionized to the hydronium ion, H3O(+), and this strongly acidic (pKa= -1.74) species effects hydration of ethene and other alkenes.

CH2=CH2 + H3O(+)——>HCH2–CH2OH + H(+)

The importance of choosing an appropriate solvent for these addition reactions should now be clear. If the addition of HCl, HBr or HI is desired, water and alcohols should not be used. These strong acids will ionize in such solvents to give ROH2(+)and the nucleophilic oxygen of the solvent will compete with the halide anions in the final step, giving alcohol and ether products. By using inert solvents such as hexane, benzene and methylene chloride, these competing solvent additions are avoided. Because these additions proceed by way of polar or ionic intermediates, the rate of reaction is greater in polar solvents, such as nitromethane and acetonitrile, than in non-polar solvents, such as cyclohexane and carbon tetrachloride.

Regioselectivity and the Markovnikov Rule

Only one product is possible from the addition of these strong acids to symmetrical alkenes such as ethene and cyclohexene. However, if the double bond carbon atoms are not structurally equivalent, as in molecules of 1-butene, 2-methyl-2-butene and 1-methylcyclohexene, the reagent conceivably may add in two different ways. This is shown for 2-methyl-2-butene in the following equation.

(CH3)2C=CHCH3 + H-Cl

(CH3)2CH–CHClCH3

or

(CH3)2CCl–CHHCH3

2-methyl-2-butene

2-chloro-3-methylbutane

2-chloro-2-methylbutane

When addition reactions to such unsymmetrical alkenes are carried out, we find that one of the two possible constitutionally isomeric products is formed preferentially. Selectivity of this sort is termedregioselectivity. In the above example, 2-chloro-2-methylbutane is nearly the exclusive product. Similarly, 1-butene forms 2-bromobutane as the predominant product on treatment with HBr.

After studying many addition reactions of this kind, the Russian chemistVladimir Markovnikovnoticed a trend in the structure of the favored addition product. He formulated this trend as an empirical rule we now callThe Markovnikov Rule: When a Brønsted acid, HX, adds to an unsymmetrically substituted double bond, the acidic hydrogen of the acid bonds to that carbon of the double bond that has the greater number of hydrogen atoms already attached to it.In more homelier vernacular this rule may be restated as, "Them that has gits."

It is a helpful exercise to predict the favored product in examples such as those shown below:

Empirical rules like the Markovnikov Rule are useful aids for remembering and predicting experimental results. Indeed, empirical rules are often the first step toward practical mastery of a subject, but they seldom constitute true understanding. The Markovnikov Rule, for example, suggests there are common and important principles at work in these addition reactions, but it does not tell us what they are. The next step in achieving an understanding of this reaction must be to construct a rational mechanistic model that can be tested by experiment.All the reagents discussed here are strong Brønsted acids so, as a first step, it seems sensible to find a base with which the acid can react. Since we know that these acids do not react with alkanes, it must be the pi-electrons of the alkene double bond that serve as the base. As shown in the diagram on the right, the pi-orbital extends into the space immediately above and below the plane of the double bond, and the electrons occupying this orbital may be attracted to the proton of a Brønsted acid. The resulting acid-base equilibrium generates a carbocation intermediate (the conjugate acid of the alkene) which then combines rapidly with the anionic conjugate base of the Brønsted acid. This two-step mechanism is illustrated for the reaction of ethene with hydrogen chloride by the following equations.

First Step: H2C=CH2 + HCl

HH2C–CH2(+) + Cl(–)

Second Step: HH2C–CH2(+)+Cl(–)

HH2C–CH2Cl

An energy diagram for this two-step addition mechanism is shown to the left. From this diagram we see that the slow or rate-determining step (the first step) is also the product determining step (the anion will necessarily bond to the carbocation site). Electron donating double bond substituents increase the reactivity of an alkene, as evidenced by the increased rate of hydration of 2-methylpropene (two alkyl groups) compared with 1-butene (one alkyl group). Evidently, alkyl substituents act to increase the rate of addition by lowering the activation energy, ΔE‡1of the rate determining step, and it is here we should look for a rationalization of Markovnikov's rule.As expected, electron withdrawing substituents, such as fluorine or chlorine, reduce the reactivity of an alkene to addition by acids (vinyl chloride is less reactive than ethene).

Energy

higher

begin

lower

George Hammond formulated a useful principle that relates the nature of a transition state to its location on the reaction path. ThisHammond Postulatestates thata transition state will be structurally and energetically similar to the species (reactant, intermediate or product) nearest to it on the reaction path. In strongly exothermic reactions the transition state will resemble the reactant species. In strongly endothermic conversions, such as that shown to the right, the transition state will resemble the high-energy intermediate or product, and will track the energy of this intermediate if it changes. This change in transition state energy and activation energy as the stability of the intermediate changes may be observed by clicking the higher or lower buttons to the right of the energy diagram. Three examples may be examined, and the reference curve is changed to gray in the diagrams for higher (magenta) and lower (green) energy intermediates.

The carbocation intermediate formed in the first step of the addition reaction now assumes a key role, in that it directly influences the activation energy for this step. Independent research shows that the stability of carbocations varies with the nature of substituents, in a manner similar to that seen for alkyl radicals. The exceptional stability of allyl and benzyl cations is the result of charge delocalization, and the stabilizing influence of alkyl substituents, although less pronounced, has been interpreted in a similar fashion.

CarbocationStability

CH3(+)

<

CH3CH2(+)

<

(CH3)2CH(+)

≈

CH2=CH-CH2(+)

<

C6H5CH2(+)

≈

(CH3)3C(+)

From this information, applying the Hammond Postulate, we arrive at a plausible rationalization of Markovnikov's rule.When an unsymmetrically substituted double bond is protonated, we expect the more stable carbocation intermediate to be formed faster than the less stable alternative, because the activation energy of the path to the former is the lower of the two possibilities. This is illustrated by the following equation for the addition of hydrogen chloride to propene. Note that the initial acid-base equilibrium leads to a pi-complex which immediately reorganizes to a sigma-bonded carbocation intermediate. The more stable 2º-carbocation is formed preferentially, and the conjugate base of the Brønsted acid (chloride anion in the example shown below) then rapidly bonds to this electrophilic intermediate to form the final product.

The following energy diagram summarizes these features. Note that the pi-complex is not shown, since this rapidly and reversibly formed species is common to both possible reaction paths.

2. Rearrangement of Carbocations

The formation of carbocations is sometimes accompanied by a structural rearrangement. Such rearrangements take place by a shift of a neighboring alkyl group or hydrogen, and are favored when the rearranged carbocation is more stable than the initial cation. The addition of HCl to 3,3-dimethyl-1-butene, for example, leads to an unexpected product, 2-chloro-2,3-dimethylbutane, in somewhat greater yield than 3-chloro-2,2-dimethylbutane, the expected Markovnikov product. This surprising result may be explained by a carbocation rearrangement of the initially formed 2º-carbocation to a 3º-carbocation by a 1,2-shift of a methyl group.

Another factor that may induce rearrangement of carbocation intermediates is strain. The addition of HCl to α-pinene, the major hydrocarbon component of turpentine, gives the rearranged product, bornyl chloride, in high yield. As shown in the following equation, this rearrangement converts a 3º-carbocation to a 2º-carbocation, a transformation that is normally unfavorable. However, the rearrangement also expands a strained four-membered ring to a much less-strained five-membered ring, and this relief of strain provides a driving force for the rearrangement. The atom numbers (colored red) for the pinene structure are retained throughout the rearrangement to help orient the viewer. The green numbers in the final product represent the proper numbering of thisbicyclic ring system.

The propensity for structural rearrangement shown by certain molecular constitutions, as illustrated above, serves as a useful probe for the intermediacy of carbocations in a reaction. We shall use this test later.

3. Addition of Lewis Acids (Electrophilic Reagents)

The proton is not the only electrophilic species that initiates addition reactions to the double bond. Lewis acids like the halogens, boron hydrides and certain transition metal ions are able to bond to the alkene pi-electrons, and the resulting complexes rearrange or are attacked by nucleophiles to give addition products. The electrophilic character of the halogens is well known. Although fluorine is uncontrollably reactive, chlorine, bromine and to a lesser degree iodine react selectively with the double bond of alkenes. The addition of chlorine and bromine to alkenes, as shown in the following general equation, proceeds by an initial electrophilic attack on the pi-electrons of the double bond. Iodine adds reversibly to double bonds, but the equilibrium does not normally favor the addition product, so it is not a useful preparative method. Dihalo-compounds in which the halogens are juxtaposed in the manner shown are calledvicinal, from the Latinvicinalis, meaning neighboring.

R2C=CR2 + X2——> R2CX-CR2X

Other halogen containing reagents which add to double bonds includehypohalous acids, HOX, and sulfenyl chlorides, RSCl. These reagents are unsymmetrical, so their addition to unsymmetrical double bonds may in principle take place in two ways. In practice, these addition reactions are regioselective, with one of the two possible constitutionally isomeric products being favored. The electrophilic moiety of these reagents is the halogen.

The regioselectivity of the above reactions may be explained by the same mechanism we used to rationalize the Markovnikov rule. Thus, bonding of an electrophilic species to the double bond of an alkene should result in preferential formation of the more stable (more highly substituted) carbocation, and this intermediate should then combine rapidly with a nucleophilic species to produce the addition product. This is illustrated by the following equation.

To apply this mechanism we need to determine the electrophilic moiety in each of the reagents.By using electronegativity differences we can dissect common addition reagents into electrophilic and nucleophilic moieties, as shown on the right. In the case of hypochlorous and hypobromous acids (HOX), these weak Brønsted acids (pKa's ca. 8) do not react as proton donors; and since oxygen is more electronegative than chlorine or bromine, the electrophile will be a halide cation. The nucleophilic species that bonds to the intermediate carbocation is then hydroxide ion, or more likely water (the usual solvent for these reagents), and the products are called halohydrins. Sulfenyl chlorides add in the opposite manner because the electrophile is a sulfur cation, RS(+), whereas the nucleophilic moiety is chloride anion (chlorine is more electronegative than sulfur).

If you understand this mechanism you should be able to write products for the following reactions:

The addition products formed in reactions of alkenes with mercuric acetate and boron hydrides (compounds shown at the bottom of of the reagent list) are normally not isolated, but instead are converted to alcohols by a substitution reaction. These important synthetic transformations are illustrated for 2-methylpropene by the following equations, in which the electrophilic moiety is colored red and the nucleophile blue. The top reaction sequence illustrates theoxymercurationprocedure and the bottom is an example ofhydroboration.

The light blue vertical line separates the addition reaction on the left from the substitution on the right. The atoms or groups that have been added to the original double bond are colored orange in the final product. In both cases the overall reaction is the addition of water to the double bond, but the regioselectivity is reversed. The oxymercuration reaction gives the product predicted by Markovnikov's rule; hydroboration on the other hand gives the "anti-Markovnikov" product. Complementary reactions such as these are important because they allow us to direct a molecular transformation whichever way is desired.Mercury and boron are removed from the organic substrate in the second step of oxymercuration and hydroboration respectively. These reactions are seldom discussed in detail; however, it is worth noting that the mercury moiety is reduced to metallic mercury by borohydride (probably by way of radical intermediates), and boron is oxidized to borate by the alkaline peroxide. Addition of hydroperoxide anion to the electrophilic borane generates a tetra-coordinate boron peroxide, having the general formula R3B-O-OH(-). This undergoes successive intramolecular shifts of alkyl groups from boron to oxygen, accompanied in each event by additional peroxide addition to electron deficient boron. The retention of configuration of the migrating alkyl group is attributed to the intramolecular nature of the rearrangement.Since the oxymercuration sequence gives the same hydration product as acid-catalyzed addition of water(see Brønsted acid addition), we might question why this two-step procedure is used at all. The reason lies in the milder reaction conditions used for oxymercuration. The strong acid used for direct hydration may not be tolerated by other functional groups, and in some cases may cause molecular rearrangement(see above).

The addition of borane, BH3, requires additional comment. In pure form this reagent is a dimeric gas B2H6, called diborane, but in ether or THF solution it is dissociated into a solvent coordinated monomer, R2O-BH3. Although diborane itself does not react easily with alkene double bonds,H.C. Brown(Purdue, Nobel Prize 1979) discovered that the solvated monomer adds rapidly under mild conditions. Boron and hydrogen have rather similar electronegativities, with hydrogen being slightly greater, so it is not likely there is significant dipolar character to the B-H bond. Since boron is electron deficient (it does not have a valence shell electron octet) the reagent itself is a Lewis acid and can bond to the pi-electrons of a double bond by displacement of the ether moiety from the solvated monomer. As shown in the following equation, this bonding might generate a dipolar intermediate consisting of a negatively-charged boron and a carbocation. Such a species would not be stable and would rearrange to a neutral product by the shift of a hydride to the carbocation center. Indeed, this hydride shift is believed to occur concurrently with the initial bonding to boron, as shown by the transition state drawn below the equation, so the discrete intermediate shown in the equation is not actually formed. Nevertheless, the carbocation stability rule cited above remains a useful way to predict the products from hydroboration reactions.Note that this addition is unique among those we have discussed, in that it is a single-step process. Also, all three hydrogens in borane are potentially reactive, so that the alkyl borane product from the first addition may serve as the hydroboration reagent for two additional alkene molecules.

To examine models of B2H6. and its dissociation in THF

Stereoselectivity in Addition Reactions to Double Bonds

As illustrated in the drawing on the right, the pi-bond fixes the carbon-carbon double bond in a planar configuration, and does not permit free rotation about the double bond itself.We see then that addition reactions to this function might occur in three different ways, depending on the relative orientation of the atoms or groups that add to the carbons of the double bond: (i) they may bond from the same side, (ii) they may bond from opposite sides, or (iii) they may bond randomly from both sides. The first two possibilities are examples ofstereoselectivity, the first being termedsyn-addition, and the secondanti-addition. Since initial electrophilic attack on the double bond may occur equally well from either side, it is in the second step (or stage) of the reaction (bonding of the nucleophile) that stereoselectivity may be imposed.If the two-step mechanism described above is correct, and if the carbocation intermediate is sufficiently long-lived to freely-rotate about the sigma-bond component of the original double bond, we would expect to find random or non-stereoselective addition in the products. On the other hand, if the intermediate is short-lived and factors such as steric hindrance or neighboring group interactions favor one side in the second step, then stereoselectivity in product formation is likely. The following table summarizes the results obtained from many studies, the formula HX refers to all the strong Brønsted acids. The interesting differences in stereoselectivity noted here provide further insight into the mechanisms of these addition reactions.

Reagent

H–X

X2

HO–X

RS–Cl

Hg(OAc)2

BH3

Stereoselectivity

mixed

anti

anti

anti

anti

syn

1. Brønsted Acid Additions

The stereoselectivity of Brønsted acid addition is sensitive to experimental conditions such as temperature and reagent concentration. The selectivity is often anti, but reports of syn selectivity and non-selectivity are not uncommon. Of all the reagents discussed here, these strong acid additions (E = H in the following equation) come closest to proceeding by the proposed two-step mechanism in which a discrete carbocation intermediate is generated in the first step. Such reactions are most prone to rearrangement when this is favored by the alkene structure.

2. Addition Reactions Initiated by Electrophilic Halogen

The halogens chlorine and bromine add rapidly to a wide variety of alkenes without inducing the kinds of structural rearrangements noted for strong acids (first example below). The stereoselectivity of these additions is stronglyanti, as shown in many of the following examples.

An important principle should be restated at this time. The alkenes shown here are all achiral, but the addition products have chiral centers, and in many cases may exist as enantiomeric stereoisomers. In the absence of chiral catalysts or reagents, reactions of this kind will always give racemic mixtures if the products are enantiomeric. On the other hand, if two chiral centers are formed in the addition the reaction will be diastereomer selective. This is clearly shown by the addition of bromine to the isomeric 2-butenes. Anti-addition to cis-2-butene gives the racemic product, whereas anti-addition to the trans-isomer gives the meso-diastereomer.We can account both for the high stereoselectivity and the lack of rearrangement in these reactions by proposing a stabilizing interaction between the developing carbocation center and the electron rich halogen atom on the adjacent carbon. This interaction, which is depicted for bromine in the following equation, delocalizes the positive charge on the intermediate and blocks halide ion attack from the syn-location.

The stabilization provided by this halogen-carbocation bonding makes rearrangement unlikely, and in a few cases three-membered cyclic halonium cations have been isolated and identified as true intermediates. A resonance description of such a bromonium ion intermediate is shown below. The positive charge is delocalized over all the atoms of the ring, but should be concentrated at the more substituted carbon (carbocation stability), and this is the site to which the nucleophile will bond.

Because they proceed by way of polar ion-pair intermediates, chlorine and bromine addition reactions are faster in polar solvents than in non-polar solvents, such as hexane or carbon tetrachloride. However, in order to prevent solvent nucleophiles from competing with the halide anion, these non-polar solvents are often selected for these reactions. In water or alcohol solution the nucleophilic solvent may open the bromonium ion intermediate to give an α-halo-alcohol or ether, together with the expected vic-dihalide. Such reactions are sensitive to pH and other factors, so when these products are desired it is necessary to modify the addition reagent. Aqueous chlorine exists as the following equilibrium, Keq≈ 10-4. By adding AgOH, the concentration of HOCl can be greatly increased, and the chlorohydrin addition product obtained from alkenes.

Cl2 + H2O

HOCl + HCl

The more widely used HOBr reagent, hypobromous acid, is commonly made by hydrolysis of N-bromoacetamide, as shown below. Both HOCl and HOBr additions occur in an anti fashion, and with the regioselectivity predicted by this mechanism (OH bonds to the more substituted carbon of the alkene).

CH3CONHBr + H2O

HOBr + CH3CONH2

Vicinal halohydrins provide an alternative route for the epoxidation of alkenes over that ofreaction with peracids. As illustrated in the following diagram, a base induced intramolecularsubstitution reactionforms a three-membered cyclic ether called an epoxide. Both the halohydrin formation and halide displacement reactions are stereospecific, so stereoisomerism in the alkene will be reflected in the epoxide product (i.e.trans-2-butene forms a trans-disubstituted epoxide). A general procedure for forming these useful compounds will be discussed in the next section.

Reactions of Alkenes Part II

3. Addition Reactions Involving Other Cyclic Onium Intermediates

Sulfenyl chloride additions are initiated by the attack of an electrophilic sulfur species on the pi-electrons of the double bond. The resulting cationic intermediate may be stabilized by the non-bonding valence shell electrons on the sulfur in exactly the same way the halogens exerted their influence. Indeed, a cyclic sulfonium ion intermediate analogous to the bromonium ion is believed to best represent this intermediate (see drawing on the left).Two advantages of the oxymercuration method of adding water to a double bond are its high anti-stereoselectivity and the lack of rearrangement in sensitive cases. These characteristics are attributed to a mercurinium ion intermediate, analogous to the bromonium ion discussed above. In this case it must be d-orbital electrons that are involved in bonding to carbon. A drawing of this intermediate is shown on the right.

Hydroboration StereoselectivityThe hydroboration reaction is among the few simple addition reactions that proceed cleanly in a syn fashion.As noted above, this is a single-step reaction. Since the bonding of the double bond carbons to boron and hydrogen is concerted, it follows thatthe geometry of this addition must be syn. Furthermore, rearrangements are unlikely inasmuch as a discrete carbocation intermediate is never formed. These features are illustrated for the hydroboration of α-pinene in the following equation. Since the hydroboration procedure is most commonly used to hydrate alkenes in an anti-Markovnikov fashion, we also need to know the stereoselectivity of the second oxidation reaction, which substitutes a hydroxyl group for the boron atom. Independent study has shown this reaction takes place withretention of configurationso the overall addition of water is also syn.

The hydroboration of α-pinene also provides a nice example of steric hindrance control in a chemical reaction. In the less complex alkenes used in earlier examples the plane of the double bond was often a plane of symmetry, and addition reagents could approach with equal ease from either side. In this case, one of the methyl groups bonded to C-6 (colored blue in the equation) covers one face of the double bond, blocking any approach from that side. All reagents that add to this double bond must therefore approach from the side opposite this methyl.

4. Hydrogenation

Addition of hydrogen to a carbon-carbon double bond is calledhydrogenation. The overall effect of such an addition is the reductive removal of the double bond functional group. Regioselectivity is not an issue, since the same group (a hydrogen atom) is bonded to each of the double bond carbons. The simplest source of two hydrogen atoms is molecular hydrogen (H2), but mixing alkenes with hydrogen does not result in any discernible reaction. Although the overall hydrogenation reaction is exothermic, a high activation energy prevents it from taking place under normal conditions. This restriction may be circumvented by the use of a catalyst, as shown in the following diagram.

Catalysts are substances that changes the rate (velocity) of a chemical reaction without being consumed or appearing as part of the product. Catalysts act by lowering the activation energy of reactions, but they do not change the relative potential energy of the reactants and products. Finely divided metals, such as platinum, palladium and nickel, are among the most widely used hydrogenation catalysts. Catalytic hydrogenation takes place in at least two stages, as depicted in the diagram. First, the alkene must be adsorbed on the surface of the catalyst along with some of the hydrogen. Next, two hydrogens shift from the metal surface to the carbons of the double bond, and the resulting saturated hydrocarbon, which is more weakly adsorbed, leaves the catalyst surface. The exact nature and timing of the last events is not well understood.As shown in the energy diagram, the hydrogenation of alkenes is exothermic, and heat is released corresponding to the ΔE (colored green) in the diagram. This heat of reaction can be used to evaluate the thermodynamic stability of alkenes having different numbers of alkyl substituents on the double bond. For example, the following table lists the heats of hydrogenation for three C5H10alkenes which give the same alkane product (2-methylbutane). Since a large heat of reaction indicates a high energy reactant, these heats are inversely proportional to the stabilities of the alkene isomers. To a rough approximation, we see that each alkyl substituent on a double bond stabilizes this functional group by a bit more than 1 kcal/mole.

Alkene Isomer

(CH3)2CHCH=CH23-methyl-1-butene

CH2=C(CH3)CH2CH32-methyl-1-butene

(CH3)2C=CHCH32-methyl-2-butene

Heat of Reaction( ΔHº )

–30.3 kcal/mole

–28.5 kcal/mole

–26.9 kcal/mole

From the mechanism shown here we would expect the addition of hydrogen to occur with syn-stereoselectivity. This is often true, but the hydrogenation catalysts may also cause isomerization of the double bond prior to hydrogen addition, in which case stereoselectivity may be uncertain.The formation of transition metal complexes with alkenes has been convincingly demonstrated by the isolation of stable platinum complexes such as Zeise's salt, K[PtCl3(C2H4)].H2O, and ethylenebis(triphenylphosphine)platinum, [(C6H5)3P]2Pt(H2C=CH2). In the latter, platinum is three-coordinate and zero-valent, whereas Zeise's salt is a derivative of platinum(II). A model of Zeise's salt and a discussion of the unusual bonding in such complexes may be viewed. Similar complexes have been reported for nickel and palladium, metals which also function as catalysts for alkene hydrogenation.

A non-catalytic procedure for the syn-addition of hydrogen makes use of the unstable compound diimide, N2H2. This reagent must be freshly generated in the reaction system, usually by oxidation of hydrazine, and the strongly exothermic reaction is favored by the elimination of nitrogen gas (a very stable compound). Diimide may exist as cis-trans isomers; only the cis-isomer serves as a reducing agent. Examples of alkene reductions by both procedures are shown on the right.

5. Oxidations

(i) Hydroxylation

Dihydroxylated products (glycols) are obtained by reaction with aqueous potassium permanganate (pH > 8) or osmium tetroxide in pyridine solution. Both reactions appear to proceed by the same mechanism (shown below); the metallocyclic intermediate may be isolated in the osmium reaction. In basic solution the purple permanganate anion is reduced to the green manganate ion, providing a nice color test for the double bond functional group. From the mechanism shown here we would expect syn-stereoselectivity in the bonding to oxygen, and regioselectivity is not an issue.When viewed in context with the previously discussed addition reactions, the hydroxylation reaction might seem implausible. Permanganate and osmium tetroxide have similar configurations, in which the metal atom occupies the center of a tetrahedral grouping of negatively charged oxygen atoms. How, then, would such a species interact with the nucleophilic pi-electrons of a double bond? A possible explanation is that an empty d-orbital of the electrophilic metal atom extends well beyond the surrounding oxygen atoms and initiates electron transfer from the double bond to the metal, in much the same fashion noted above for platinum. Back-bonding of the nucleophilic oxygens to the antibonding π*-orbital completes this interaction. The result is formation of a metallocyclic intermediate, as shown below.

(ii) Epoxidation

Some oxidation reactions of alkenes give cyclic ethers in which both carbons of a double bond become bonded to the same oxygen atom. These products are calledepoxidesoroxiranes. An important method for preparing epoxides is by reaction with peracids, RCO3H. The oxygen-oxygen bond of such peroxide derivatives is not only weak (ca. 35 kcal/mole), but in this case is polarized so that the acyloxy group is negative and the hydroxyl group is positive (recall that the acidity of water is about ten powers of ten weaker than that of a carboxylic acid). If we assume electrophilic character for the OH moiety, the following equation may be written.

It is unlikely that a dipolar intermediate, as shown above, is actually formed. The epoxidation reaction is believed to occur in a single step with a transition state incorporating all of the bonding events shown in the equation. Consequently, epoxidations by peracids always have syn-stereoselectivity, and seldom give structural rearrangement. You may see the transition state . Presumably the electron shifts indicated by the blue arrows induce a charge separation that is immediately neutralized by the green arrow electron shifts.

The previous few reactions have been classified as reductions or oxidations, depending on thechange in oxidation state of the functional carbons. It is important to remember that whenever an atom or group is reduced, some other atom or group is oxidized, and a balanced equation must balance the electron gain in the reduced species with the electron loss in the oxidized moiety, as well as numbers and kinds of atoms. Starting from an alkene (drawn in the box), the following diagram shows a hydrogenation reaction on the left (the catalyst is not shown) and an epoxidation reaction on the right. Examine these reactions, and for each identify which atoms are reduced and which are oxidized.

Epoxides may be cleaved by aqueous acid to give glycols that are often diastereomeric with those prepared by thesyn-hydroxylation reactiondescribed above. Proton transfer from the acid catalyst generates the conjugate acid of the epoxide, which is attacked by nucleophiles such as water in the same way that the cyclic bromonium ion described above undergoes reaction. The result isanti-hydroxylationof the double bond, in contrast to the syn-stereoselectivity of the earlier method. In the following equation this procedure is illustrated for a cis-disubstituted epoxide, which, of course, could be prepared from the corresponding cis-alkene. This hydration of an epoxide does not change the oxidation state of any atoms or groups.

(iii) Oxidative Cleavage of Double Bonds

OzonolysisIn determining the structural formula of an alkene, it is often necessary to find the location of the double bond within a given carbon framework. One way of accomplishing this would be to selectively break the double bond and mark the carbon atoms that originally formed that bond. For example, there are three isomeric alkenes that all give 2-methylbutane on catalytic hydrogenation. These are 2-methyl-2-butene (compound A), 3-methyl-1-butene (compound B) and 2-methyl-1-butene (compound C), shown in the following diagram. If the double bond is cleaved and the fragments marked at the cleavage sites, the location of the double bond is clearly determined for each case. A reaction that accomplishes this useful transformation is known.

Ozone, O3, is an allotrope of oxygen that adds rapidly to carbon-carbon double bonds. Since the overall change in ozonolysis is more complex than a simple addition reaction, its mechanism has been extensively studied. Reactive intermediates called ozonides have been isolated from the interaction of ozone with alkenes, and these unstable compounds may be converted to stable products by either a reductive workup (Zn dust in water or alcohol) or an oxidative workup (hydrogen peroxide). The chief difference in these conditions is that reductive workup gives an aldehyde product when hydrogen is present on a double bond carbon atom, whereas oxidative workup gives a carboxylic acid or carbon dioxide in such cases. The following equations illustrate ozonide formation, a process that is believed to involve initial syn-addition of ozone, followed by rearrangement of the extremely unstable molozonide addition product. They also show the decomposition of the final ozonide to carbonyl products by either a reductive or oxidative workup.

From this analysis and the examples given here, you should be able to deduce structural formulas for the alkenes that give the following ozonolysis products.

The relatively stable ozonide, arterolane, is a component of a new antimalerial drug, Synriam. Combined with piperaquine, it provides effective treatment ofPlasmodium falciparum, the most lethal form of malaria. The ozonide ring is similar to the bridged trioxide unit found in the Chinese herb artemisinin and its derivative artemether, which, combined with lumafantrine have also been used as the antimalerial drug, Coartem. Traditional medications such as chloroquine are effective in only 50 percent of patients where the parasite is drug-resistant.

Glycol CleavageThe vicinal glycols prepared by alkene hydroxylation (reaction with osmium tetroxide or permanganate) are cleaved to aldehydes and ketones in high yield by the action oflead tetraacetate(Pb(OAc)4) orperiodic acid(HIO4). This oxidative cleavage of a carbon-carbon single bond provides a two-step, high-yield alternative to ozonolysis, that is often preferred for small scale work involving precious compounds. A general equation for these oxidations is shown below. As a rule, cis-glycols react more rapidly than trans-glycols, and there is evidence for the intermediacy of heterocyclic intermediates (as shown), although their formation is not necessary for reaction to occur.

Practice Problems

The following problems review many aspects of alkene chemistry. The first question allows you to choose the form of the question (i.e. starting alkene, reagent or product). The second question requires you to draw the product of a reaction selected from 54 possible combinations of alkene and reagent. The third question asks you to choose reagents which will convert propene into a designated product (more than one step may be needed). The fourth question is another reagent selection problem (the ketone can be ignored), and the fifth is similar but also requires selecting the starting alkene for the synthesis. The next two problems concern the ozonolysis cleavage of double bonds. The eighth question concerns four reactions in which stereospecific addition reactions have taken place. Finally, a random quiz may be examined.

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Free Radical Reactions

Free Radical Reactions of Alkenes

1. Addition of Radicals to Alkenes

Protons and other electrophiles are not the only reactive species that initiate addition reactions to carbon-carbon double bonds. Curiously, this first became evident as a result of conflicting reports concerning the regioselectivity of HBr additions. As noted earlier, the acid-induced addition of HBr to 1-butene gave predominantly 2-bromobutane, theMarkovnikov Ruleproduct. However, in some early experiments in which peroxide contaminated reactants were used, 1-bromobutane was the chief product. Further study showed that an alternative radical chain-reaction, initiated by peroxides, was responsible for the anti-Markovnikov product. This is shown by the following equations.

The weak O–O bond of a peroxide initiator is broken homolytically by thermal or hight energy. The resulting alkoxy radical then abstracts a hydrogen atom from HBr in a strongly exothermic reaction. Once a bromine atom is formed it adds to the π-bond of the alkene in the first step of a chain reaction. This addition is regioselective, giving the more stablecarbon radicalas an intermediate. The second step is carbon radical abstraction of another hydrogen from HBr, generating the anti-Markovnikov alkyl bromide and a new bromine atom. Each of the steps in this chain reaction is exothermic, so once started the process continues until radicals are lost to termination events.This free radical chain addition competes very favorably with the slower ionic addition of HBr described earlier, especially in non-polar solvents. It is important to note, however, that HBr is unique in this respect. The radical addition process is unfavorable for HCl and HI because one of the chain steps becomes endothermic (the second for HCl & the first for HI).Other radical addition reactions to alkenes have been observed, one example being the peroxide induced addition of carbon tetrachloride shown in the following equation

RCH=CH2 + CCl4 (peroxide initiator) —> RCHClCH2CCl3

The best known and most important use of free radical addition to alkenes is probablypolymerization. Since the addition of carbon radicals to double bonds is energetically favorable, concentrated solutions of alkenes are prone to radical-initiated polymerization, as illustrated for propene by the following equation. The blue colored R-group represents an initiating radical species or a growing polymer chain; the propene monomers are colored maroon. The addition always occurs so that the more stable radical intermediate is formed.

2. Allylic Substitution

We noted earlier that benzylic and allylic sites are exceptionally reactive infree radical halogenation reactions. Since carbon-carbon double bonds add chlorine and bromine in liquid phase solutions, radical substitution reactions by these halogens are often carried out at elevated temperature in the gas phase (first equation below). Formation of the ionic π-complexes that are intermediates in halogen addition is unfavorable in the absence of polar solvents, andentropygenerally favors substitution over addition.The brominating reagent, N-bromosuccinimide (NBS), has proven useful for achieving allylic or benzylic substitution in CCl4solution at temperatures below its boiling point (77 ºC). One such application is shown in the second equation.

The predominance of allylic substitution over addition in the NBS reaction is interesting. The N–Br bond is undoubtedly weak (probably less than 50 kcal/mol) so bromine atom abstraction by radicals should be very favorable. The resulting succinimyl radical might then establish a chain reaction by removing an allylic hydrogen from the alkene. One problem with this mechanism is that NBS is very insoluble in CCl4, about 0.006 mole / liter at reflux. Although it is possible that the allylic bromination occurs at a solid-liquid interface, evidence for another pathway has been obtained. In the non-polar solvent used for these reactions, very low concentrations of bromine may be generated from NBS. This would serve as a source of bromine atoms, which would abstract allylic hydrogens irreversibly (an exothermic reaction) in competition with reversible addition to the double bond. The HBr produced in this way is known to react with NBS, giving a new bromine molecule and succinimide, as shown here. Ionic addition of bromine to the double bond would be very slow in these circumstances (CCl4is a nonpolar solvent).

HBr + (CH2CO)2NBr —> Br2 + (CH2CO)2NH

This mechanism is essentially the same as that for thefree radical halogenationof alkanes, with NBS serving as a source of very low concentrations of bromine. Unsymmetrical allylic radicals will react to give two regioisomers. Thus, 1-octene on bromination with NBS yields a mixture of 3-bromo-1-octene (ca. 18%) and 1-bromo-2-octene (82%) - both cis and trans isomers.

RCH2CH=CH2 + (CH2CO)2NBr—> RCHBrCH=CH2 + RCH=CHCH2Br + (CH2CO)2NH

Dienes

Dienes

1. Properties of Dienes

When considering compounds having two or more double bonds in a molecule, it is useful to identify three distinct ways in which these functions may be oriented with respect to each other. First, the double bonds may be separated by one or more sp3-hybridized carbon atoms, as in 1,5-hexadiene. In this circumstance each double bond behaves independently of the other, and we refer to them asisolated. A second relationship has the double bonds connected to each other by a single bond, as in 1,3-hexadiene, and we refer to this arrangement asconjugated. Finally, two double bonds might share a carbon atom, as in 1,2-hexadiene. The central carbon atom in such a system is sp-hybridized, and we call such double bondscumulated. These three isomers are shown in the following diagram, and three other similar isomers will be displayed on . In cases where stereoisomers are possible only the E-isomer is shown.Another stereoisomeric factor associated with conjugated dienes will be demonstrated. Rotation about the single bond joining the two double bonds (colored blue) converts a trans-likes-transconformation to itss-cisform. The energy barrier to this conformational isomerization is normally low, and the s-trans conformer is often more stable than the s-cis conformer, as shown in the diagram.

These categories are based on more than obvious structural variations. We find significant differences in the chemical properties of dienes depending on their structural type.For example, catalytic hydrogenation converts all the dienes shown here to the alkane hexane, but the heats of reaction (heat of hydrogenation) reflect characteristic differences in their thermodynamic stability. This is illustrated in the diagram on the right. Taking the heat of hydrogenation of 1-hexene (30.1 kcal/mole) as a reference, we find that the isolated diene, 1,5-hexadiene, as expected, generates double this heat of reaction on conversion to hexane. The cumulated diene, 1,2-hexadiene, has a 6 kcal/mole higher heat of reaction, indicating it is less stable than the isolated diene by this magnitude. On the other hand, conjugation of double bonds seems to stabilize a diene by about 5 kcal/mole. The increase in stability of 2,4-hexadiene over 1,3-hexadiene (both are conjugated) is due to the increased double bond substitution of the former, a factor notedearlierfor simple alkenes.The stabilization of dienes by conjugation is less dramatic than thearomatic stabilization of benzene. Nevertheless, similar resonance and molecular orbital descriptions of conjugation may be written. A resonance description, such as the one shown here, involves charge separation, implying a relatively small degree of stabilization.

CH2=CH-CH=CH2(+)CH2-CH=CH-CH2:(–)

A molecular orbital model for 1,3-butadiene is shown below. Note that the lobes of the four p-orbital components in each pi-orbital are colored differently and carry a plus or minus sign. This distinction refers to different phases, defined by the mathematical wave equations for such orbitals. Regions in which adjacent orbital lobes undergo a phase change are callednodes. Orbital electron density is zero in such regions. Thus a single p-orbital has a node at the nucleus, and all the pi-orbitals shown here have a nodal plane that is defined by the atoms of the diene. This is the only nodal surface in the lowest energy pi-orbital, π1. Higher energy pi-orbitals have an increasing number of nodes.

To examine a model of the p-orbital components for the s-cis conformer of a 1,3-diene.

To examine the molecular orbitals of both s-trans and s-cis-1,3-butadiene

2. Addition Reactions of Dienes

Addition reactions of isolated dienes proceed more or less as expected from the behavior of simple alkenes. Thus, if one molar equivalent of 1,5-hexadiene is treated with one equivalent of bromine a mixture of 5,6-dibromo-1-hexene, 1,2,5,6-tetrabromohexane and unreacted diene is obtained, with the dibromo compound being the major product (about 50%).

CH2=CH(CH2)2CH=CH2+ Br2

BrCH2CHBr(CH2)2CH=CH2+

BrCH2CHBr(CH2)2CHBrCH2Br +

CH2=CH(CH2)2CH=CH2

5,6-dibromo-1-hexene

1,2,5,6-tetrabromohexane

1,5-hexadiene

Similar reactions of conjugated dienes, on the other hand, often give unexpected products. The addition of bromine to 1,3-butadiene is an example. As shown below, a roughly 50:50 mixture of 3,4-dibromo-1-butene (the expected product) and 1,4-dibromo-2-butene (chiefly the E-isomer) is obtained. The latter compound is remarkable in that the remaining double bond is found in a location where there was no double bond in the reactant. This interesting relocation requires an explanation.

CH2=CH-CH=CH2+ Br2

BrCH2CHBr-CH=CH2+

BrCH2CH=CHCH2Br

3,4-dibromo-1-butene

1,4-dibromo-2-butene

The expected addition product from reactions of this kind is the result of1,2-addition, i.e. bonding to the adjacent carbons of a double bond. The unexpected product comes from1,4-addition, i.e. bonding at the terminal carbon atoms of a conjugated diene with a shift of the remaining double bond to the 2,3-location. These numbers refer to the four carbons of the conjugated diene and are not IUPAC nomenclature numbers. Product compositions are often temperature dependent, as the addition of HBr to 1,3-butadiene demonstrates.

CH2=CH-CH=CH2+ HBr reaction temperature

CH3CHBr-CH=CH2+1,2 addition yield

CH3CH=CHCH2Br1,4 addition yield

0 ºC40 ºC

70%15%

30%85%

Bonding of an electrophilic atom or group to one of the end carbon atoms of a conjugated diene (#1) generates an allyl cation intermediate. Such cations are stabilized by charge delocalization, and it is this delocalization that accounts for the 1,4-addition product produced in such addition reactions. As shown in the diagram, the positive charge is distributed over carbons #2 and #4 so it is at these sites that the nucleophilic component bonds. Note that resonance stabilization of the allyl cation is greater than comparablestabilization of 1,3-butadiene, because charge is delocalized in the former, but created and separated in the latter.

An explanation for the temperature influence is shown in the following energy diagram for the addition of HBr to 1,3-butadiene. The initial step in which a proton bonds to carbon #1 is therate determining step, as indicated by the large activation energy (light gray arrow). The second faster step is theproduct determining step, and there are two reaction paths (colored blue for 1,2-addition and magenta for 1,4-addition). The 1,2-addition has a smaller activation energy than 1,4-addition, but the 1,4-product is more stable than the 1,2-product. At low temperatures, the products are formed irreversibly and reflect the relative rates of the two competing reactions. This is termedkinetic control. At higher temperatures, equilibrium is established between the products, and thethermodynamically favored1,4-product dominates.

3. Diels-Alder Cycloaddition

The unique character of conjugated dienes manifests itself dramatically in theDiels-AlderCycloaddition Reaction. A cycloaddition reaction is the concerted bonding together of two independent pi-electron systems to form a new ring of atoms. When this occurs, two pi-bonds are converted to two sigma-bonds, the simplest example being the hypothetical combination of two ethene molecules to give cyclobutane. This does not occur under normal conditions, but the cycloaddition of 1,3-butadiene to cyanoethene (acrylonitrile) does, and this is an example of the Diels-Alder reaction. The following diagram illustrates two cycloadditions, and introduces several terms that are useful in discussing reactions of this kind.

In the hypothetical ethylene dimerization on the left, each reactant molecule has a pi-bond (colored orange) occupied by two electrons. The cycloaddition converts these pi-bonds into new sigma-bonds (colored green), and this transformation is then designated a [2+2] cycloaddition, to enumerate the reactant pi-electrons that change their bonding location.The Diels-Alder reaction is an important and widely used method for making six-membered rings, as shown on the right. The reactants used in such reactions are a conjugated diene, simply referred to as thediene, and a double or triple bond coreactant called thedienophile, because it combines with (has an affinity for) the diene. The Diels-Alder cycloaddition is classified as a [4+2] process because the diene has four pi-electrons that shift position in the reaction and the dienophile has two.The Diels-Alder reaction is a single step process, so the diene component must adopt a cis-like conformation in order for the end carbon atoms (#1 & #4) to bond simultaneously to the dienophile. Such conformations are calleds-cis, thesreferring to the single bond connecting the two double bonds. The s-cis and s-trans conformers of 1,3-butadiene are shown in the preceding diagram. For many acyclic dienes the s-trans conformer is more stable than the s-cis conformer (due to steric crowding of the end groups), but the two are generally in rapid equilibrium, permitting the use of all but the most hindered dienes as reactants in Diels-Alder reactions. In its usual form, the diene component is electron rich, and the best dienophiles are electron poor due to electron withdrawing substituents such as CN, C=O & NO2. The initial bonding interaction reflects this electron imbalance, with the two new sigma-bonds being formed simultaneously, but not necessarily at equal rates.

Stereospecificity

We noted earlier that addition reactions of alkenes often exhibitedstereoselectivity, in that the reagent elements in some cases added syn and in other cases anti to the the plane of the double bond. Both reactants in the Diels-Alder reaction may demonstrate stereoisomerism, and when they do it is found that the relative configurations of the reactants are preserved in the product (the adduct). The following drawing illustrates this fact for the reaction of 1,3-butadiene with (E)-dicyanoethene. The trans relationship of the cyano groups in the dienophile is preserved in the six-membered ring of the adduct. Likewise, if the terminal carbons of the diene bear substituents, their relative configuration will be retained in the adduct. Using the earlier terminology, we could say that bonding to both the diene and the dienophile is syn. An alternative description, however, refers to the planar nature of both reactants and terms the bonding in each case to besuprafacial(i.e. to or from the same face of each plane). Thisstereospecificityalso confirms the synchronous nature of the 1,4-bonding that takes place.

The essential characteristics of the Diels-Alder cycloaddition reaction may be summarized as follows:

(i)The reaction always creates a new six-membered ring. When intramolecular, another ring may also be formed.(ii)The diene component must be able to assume a s-cis conformation.(iii)Electron withdrawing groups on the dienophile facilitate reaction.(iv)Electron donating groups on the diene facilitate reaction.(v)Steric hindrance at the bonding sites may inhibit or prevent reaction.(vi)The reaction is stereospecific with respect to substituent configuration in both the dienophile and the diene.

These features are illustrated by the following eight examples, one of which does not give a Diels-Alder cycloaddition. Try to predict the course of each reaction before disclosing the answers by pressing the "Show Products" button. The formation of a new six-membered ring should be apparent in every case where reaction occurs.

There is no reaction in exampleDbecause this diene cannot adopt a s-cis orientation. In examplesB, C, F, G & Hat least one of the reactants is cyclic so that the product has more than one ring, but the newly formed ring is always six-membered. In exampleBthe the same cyclic compound acts as both the diene colored blue) and the dienophile (colored red). The adduct has three rings, two of which are the five-membered rings present in the reactant, and the third is the new six-membered ring (shaded light yellow). ExampleChas an alkyne as a dienophile (colored red), so the adduct retains a double bond at that location. This double bond could still serve as a dienophile, but in the present case the diene is sufficiently hindered to retard a second cycloaddition. The quinone dienophile in reactionFhas two dienophilic double bonds. However, the double bond with two methyl substituents is less reactive than the unsubstituted dienophile due in part to the electron donating properties of the methyl groups and in part to steric hindrance. The stereospecificity of the Diels-Alder reaction is demonstrated by examplesA, E & H. InA & Hthe stereogenic centers lie on the dienophile, whereas inEthese centers are on the diene. In all cases the configuration of the reactant is preserved in the adduct.

Cyclic dienes, such as those in examplesB, C & G, givebridged bicyclicadducts for which an additional configurational feature must be designated. As shown in the following diagram, there are two possible configurations for compounds of this kind. If a substituent (colored magenta here) is oriented cis to the longest or more unsaturated bridge (colored blue here), it is said to beendo. When directed trans to the bridge it isexo. When the Diels-Alder reaction forms bridged bicyclic adducts and an unsaturated substituent is located on this bicyclic structure (as inB & G), the chief product is normally the endo isomer "Alder's Endo Rule". ExampleCdoes not merit such a nomenclature, since stereoisomeric orientations of the substituent are not possible.